The candidate's overall research goal is to pursue the development of a male hormonal contraceptive and to further the understanding of male reproductive physiology as it pertains to fertility. To achieve this goal, the candidate proposes a 4-year plan comprised of 2 clinical trials and a program of didactic instruction, which will provid the training necessary for the development of an independent academic research career. The candidate, Dr. Mara Roth, has been prepared for this pathway by completing her medical doctorate and subsequent specialty and subspecialty training in Internal Medicine and Endocrinology. This research will be conducted at the Center for Research in Reproduction and Contraception, run by Dr. William Bremner, an internationally renowned expert in the field of male reproductive endocrinology and a pioneer in the development of a male hormonal contraceptive. This research will be overseen by an expert mentoring committee with several members in the Department of Medicine and Division of Endocrinology, as well as external advisors in the Departments of Urology, Obstetrics and Gynecology, and Epidemiology. Unintended pregnancies and unsafe pregnancy terminations continue to put women's lives at risk despite extensive contraceptive options for women. In addition, male contraceptive options have scarcely advanced beyond the development of condoms centuries ago, and the development of the vasectomy procedure in the early 20th century. While a goal of reproductive endocrinologists for decades, the development of a safe, effective, reversible male hormonal contraceptive has remained elusive due to a lack of uniform efficacy in all men. The goal of this research proposal is to build on the candidate's prior research by working to define the intratesticular hormonal characteristics required for spermatogenesis, which will help target the challenge of developing a more effective male hormonal contraceptive regimen. In addition, the knowledge gained in intratesticular hormonal physiology may then help to identify more effective and less invasive treatments for male infertility. The specific aims of this proposal are: 1) to define the minimum intratesticular testosterone concentration necessary for spermatogenesis in men; 2) to identify if variation in intratesticular hormone concentrations correlates with a diagnosis of infertility. The proposed studies utilize a specific procedure to obtain intratesticulr fluid, a testicular fine---needle aspiration, which avoids the risks of a testicular biopsy, but stll allows for accurate analysis of the intratesticular hormones. The clinical trials described in this proposal, coupled with didactic training and workshops in career development, provide the skills and expertise necessary for an independent investigative career.